The cytokine family of proteins exhibit a wide variety of functions. A hallmark feature is their ability to elicit chemotactic migration of distinct cell types, including polymorphonuclear cells and macrophages. Many cytokines have pro-inflammatory activity and are involved in multiple steps during inflammatory reactions. In addition to their involvement in inflammation, cytokines have been shown to exhibit other activities. For example, interleukin-8 (IL-8) promotes proliferation of keratinocytes.
In light of the diverse biological activities, it is not surprising that cytokines have been implicated in a number of physiological and disease conditions, including lymphocyte trafficking, wound healing, hematopoietic regulation and immunological disorders such as allergy, asthma and arthritis.
The protein of the present invention is a secreted protein, similar to cytokine proteins, and is most homologous at the amino acid level to the fringe (fng) gene of Drosophila.
The fringe (fng) gene, encodes a molecule that mediates signaling between distinct cell populations (Irvine, K. D. and Wieschaus, E., Cell, 79: 595-506 (1994). The fng gene encodes a putatively secreted protein, and mediates processes that establish the wing margin and promote wing outgrowth without otherwise affecting dorsal-ventral wing cell identity.
The fng cDNA includes a 412 codon open reading frame encoding for a novel protein. Notably, this predicted protein product includes a signal sequence at its amino-terminal end but lacks predicted transmembrane domains, suggesting that it is secreted (Kyte J. and Doolittle, R. F., J. Mol. Biol., 157: 105-132 (1982); Eisenberg, D., et al., J. Mol. Biol., 179: 125-142 (1984); von Heijne, G., Nucl. Acids Res. 14: 4583-4690 (1986)). fng may have a role in cell-cell interactions promoting wing margin formation and wing growth. The fng gene affects a class of epithelial cells which ultimately form the wing. This is done by altering the differentiation state of the cells and enhancing their proliferation.